1. Field of the Invention
THIS INVENTION relates to osteoinductive biomaterials. In particular the invention relates to an osteogenic composition and to the use of an osteogenic composition in therapy.
2. Description of Related Art
The osteogenic composition of the invention is particularly intended for human or mammalian tissue regeneration and for promoting or inducing bone growth. For the purposes of this specification, the phrase “osteogenic protein” refers to the material which is obtained by fractionation of total mammalian bone protein and which is capable of inducing bone formation. The terms “osteogenic” and “osteoinductive” are considered to be synonymous. Osteogenesis is the term used to describe the de novo formation of bone in adult mammals and is evidenced in adults during regeneration of bone fractures. It proceeds via a process which closely resembles embryonic osteogenesis. Osteogenic protein contains, amongst other unidentified proteins, Bone Morphogenetic Proteins (BMPs). This is a family of characterized proteins which have been classified as part of the larger transforming growth factor-beta superfamily of morphogenic proteins. The BMP family comprises more than a dozen individual members which are known to be capable of inducing bone formation in mammals.
Mammalian bone tissue is host to a family of protein growth and differentiation factors, called the bone morphogenetic proteins (BMPs). These proteins are capable of inducing new bone formation when implanted in adolescent and adult mammals.
The BMPs are redeployed in adults to cause regeneration of bone via mechanisms closely resembling embryonic differentiation. The developmental cascade of bone differentiation consists of chemotaxis of mesenchymal cells, proliferation of progenitor cells, differentiation of cartilage, vascular invasion, bone formation, remodeling, and finally marrow differentiation (Reddi, (1981) Collagen Rel. Res. 1:209-226). It has been shown that the natural endochondral bone differentiation activity of bone matrix can be dissociatively extracted and reconstituted with inactive residual matrix to restore full bone inductive activity (Sampath and Reddi, (1981) Proc. Natl. Acad. Sci. USA 78:7599-7603). The purification of osteogenin, an osteogenic protein from mammalian bone is disclosed by Sampath et al. (1987) (Proc. Natl. Acad. Sci. USA 84, 7109-7113). Urist et al. (Proc. Natl. Acad. Sci. USA (1984) 81:371-375) disclose a bovine bone morphogenetic protein extract having the properties of an acidic polypeptide and a molecular weight of approximately 18 kD. The authors report that the protein is present in a fraction separated by hydroxyapatite chromatography, and that it induces bone formation in mouse hindquarter muscle and bone regeneration in trephone defects in rat and dog skulls.
European Patent Application No. 148,155, published Oct. 7, 1985, discloses osteogenic proteins derived from bovine, porcine, and human origin. One of the proteins, designated by the inventors as a P3 protein and having a molecular weight of 22-24 kD, is reported to have been purified to an essentially homogeneous state. This material is reported to induce bone formation when implanted into animals.